Evaluation of amentoflavone metabolites on PARP-1 inhibition and the potentiation on anti-proliferative effects of carboplatin in A549 cells

The present study aims to determine the major metabolites of amentoflavone (AMF) and further evaluate their inhibitory effects on PARP-1. First, different fractions (Frs. 1-9), which were collected according to retention time of AMF metabolites based on UHPLC-QTOF-MS/MS qualitative analysis, were evaluated on their inhibitory effects against PARP-1. Then, two mono-sulfate metabolites in the fractions with potent PARP-1 inhibitory effect were targetedly semi-synthesized. Moreover, three mono-sulfate conjugates (compound 8, 9 and 10), including one disulfate conjugate (compound 10), were isolated and their structures were fully elucidated by UHPLCQTOF-MS/MS and NMR. Finally, the binding mode of compound 8 (amentoflavone-4 '''-O-sulfate) toward PARP-1 and its potentiation on carboplatin (CBP) in A549 cells were investigated. This study was the first report on bioactivity evaluation of AMF metabolites in rat bile on PARP-1 and the potentiation of compound 8 on carboplatin (CBP) in A549 cells in vitro. This paper also provided scientific basis for the AMF metabolites on PARP-1 inhibition and chemosensitization.

Automated summary

This study evaluated the bioactivity of amentoflavone metabolites in rat bile on PARP-1 for the first time, and found that one of the metabolites sensitized carboplatin in A549 cells. The results provided a scientific basis for the inhibition of PARP-1 and chemosensitization by amentoflavone metabolites.